Uchida, Koji; Shibata, Takahiro; Toyokuni, Shinya; Daniel, Bareket; Žarković, Kamelija; Žarković, Neven; Sasson, Shlomo (2018) Development of a novel monoclonal antibody against 4-hydroxy-2E,6Z-dodecadienal (4-HDDE)-protein adducts: Immunochemical application in quantitative and qualitative analyses of lipid peroxidation in vitro and ex vivo. Free Radical Biology and Medicine, 124 . pp. 12-20. ISSN 0891-5849
Abstract
Non-enzymatic peroxidation of polyunsaturated fatty acids (PUFA) results in the formation of various α, β-unsaturated aldehydes, of which 4-hydroxyalkenals are abundant. The propensity of n-6 PUFA, such as linoleic acid, γ-linolenic acid and arachidonic acid, to undergo radical-induced peroxidation and generate 4-hydroxy-2Enonenal (4-HNE) has been widely demonstrated. The ability of the latter to form covalent adducts with macromolecules and modify cellular functions has been linked to numerous pathological processes. Concomitantly, evidence has accumulated on specific signaling properties of low concentrations of 4-HNE that may induce hormetic and protective responses to peroxidation stress in cells. It has long been known that peroxidation of PUFA, and particularly arachidonic acid, also give rise to 4-hydroxy-2E, 6Z-dodecadienal (4-HDDE), which is more chemically reactive than 4-HNE. Few studies on 4-HDDE revealed its ability to avidly interact covalently with electronegative moieties in macromolecules and to its ability to selectively activate the transcriptional regulator Peroxisome Proliferator-Activated Receptor (PPAR)-β/δ. The research on 4-HDDE has been impeded due to the lack of available pure 4-HDDE and antibodies that recognize 4-HDDE-modified epitopes in proteins. The purpose of this study was to employ an established procedure to synthesize 4-HDDE and use it to create and characterize a monoclonal antibody against 4-HDDE- modified proteins and establish its application for ELISA and immunohistochemical analysis of cells and tissues and further expand lipid peroxidation research.
| Item Type: | Article |
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| Additional Information: | Collaboration between the authors of the study presented was carried through the networking activities of the International 4-Hydroxynonenal Club. Technical assistance of Mr. Ryo Asano (Nagoya University, Japan), Mrs. Tea Vukovic and Mrs. Tea Keckes (LabOS, IRB, Zagreb, Croatia) is kindly acknowledged. This work was supported in part by Grant-in-Aid for Scientific Research (A) (No. 26252018) (K.U.) and Grant-in-Aid for Scientific Research on Innovative Areas "Oxygen Biology: a new criterion for integrated understanding of life" (No. 26111011) (K.U.) both of the Ministry of Education, Sciences, Sports and Technology (MEXT), Japan, and grants from Israel Ministry of Health (2009; Sh.S.), the David R. Bloom Center for Pharmacy at the Hebrew University of Jerusalem (2011; Sh.S.) and the Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem (2013; Sh.S.). COST (European Cooperation in Science and Technology) Actions B35, BM0602, CM1001 and BM1203 supported Sh.S and N.Z. Sh.S. is the Adolf D. and Horty Storch Chair in Pharmaceutical Sciences at the Faculty of Medicine, and is affiliated with the David R. Bloom Center for Pharmacy and the Dr. Adolf and Klara Brettler Center for Research of Molecular Pharmacology and Therapeutics in the Hebrew University of Jerusalem, Israel. |
| Uncontrolled Keywords: | Atherosclerosis ; 4-HDDE 4-HDDE-protein adducts; Lipid peroxidation ;Monoclonal antibody ;Renal failure |
| Subjects: | BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences |
| Divisions: | Division of Molecular Medicine |
| Depositing User: | Tea Vuković |
| Date Deposited: | 04 May 2020 08:49 |
| URI: | http://fulir.irb.hr/id/eprint/5680 |
| DOI: | 10.1016/j.freeradbiomed.2018.05.079 |
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